Understanding the behavioral and molecular changes that occur with normal aging is important in studying age-related cognitive dysfunction not associated with any neuropathological diseases. Neuron counts, number of synapses, and the biophysical properties of neurons have all been investigated in the brains of aged rodents, nonhuman primates, and humans, to determine if changes in these areas cause memory deficits during aging. Thus far, there does not seem to be significant changes in these areas that would explain these memory deficits. Other studies have investigated the levels of specific proteins such protein kinase C and synaptic proteins of young and aged rats in order to explain age-related memory deficits. Most of the studies have used the Morris water maze spatial task, a task known to be hippocampally-associated. However, the hippocampus is also important in processing temporally discontiguous stimuli in tasks such as trace fear conditioning. In trace fear conditioning, the subject learns to associate a neutral conditioned stimulus (CS) and an aversive unconditioned stimulus (US) with a silent "trace interval" existing between the CS and US. The long term goal of this application is to investigate the protein expression of extracellular-signal regulated kinases (ERK) and cAMP responsive element binding (CREB) proteins in young and aged rats trained in trace fear conditioning as well as the importance of ERK in trace fear conditioning. In Specific Aim 1, experiments will investigate whether aged rats are impaired in trace fear conditioning. In Specific Aim 2A, experiments will investigate whether ERK protein expression is altered in aged rats trained in trace fear conditioning. In Specific Aim 2B, experiments will investigate whether CREB protein expression is altered in aged rats trained in trace fear conditioning. In Specific Aim 3, experiments will the effects of ERK inhibition on learning and CREB phosphorylation in young rats trained in trace fear conditioning. The central hypothesis is that aged rats are impaired in trace fear conditioning because of altered levels of ERK and CREB proteins. These studies are expected to increase our knowledge of the cellular and molecular mechanisms that may underlie age-related deficits in learning and memory. Such an outcome is expected to benefit our understanding of how normal aging affects learning and memory processes.